Studies are continuing on the Philly mouse which develops a dominantly inherited cataract. The cataract is visible by 35 days of age. Microscopic changes in the lens occur much earlier and include failure of lens fiber cells to elongate. We have been investigating several facets of cataract development in the Philly mouse including the composition of crystallin proteins at different stages in lens growth, synthesis and translational efficiencies of lens mRNAs, and phase transition temperatures in the Philly mouse and F1 heterozygote. 2-D gel electrophoresis of Philly mouse lens proteins indicate a specific deficiency of a 27K basic Beta-crystallin and its functional mRNA. Interestingly, a unique more acidic 26K protein and its functional mRNA is present. The relationship between these two proteins is now being investigated using a BetaBp cDNA probe. The behavior of the lens cytoplasm phase transition temperature (Tc) was different in the Swiss-Webster, Philly, and Swiss Webster x Philly heterozygotes. The slope (dTc/dt) changes from negative to positive on day 27 for the Philly and day 38 for the hybrid, just prior to cataract in these animals. The slope continues to be negative in the Swiss Webster. The change in slope is a graphical confirmation of the disturbance in lens cell composition and an early indicator of conditions which lead to opacity.